The goal of Project 1 is to assess the immune status of the mice that form the focus of this Program Project, i.e. the 600 UM-HET3 mice in Population 1 and the 180 genotype-selected mice in Population 2. The test battery includes the following components: . Production of anti-erythrocyte antibodies at 4 and again at 15 months of age. . Quantitation of six T cell subsets (CD4 and CD8, CD4 and CD8 memory, and the CD4P and CD8P subsets that express cell surface P-glycoprotein) in blood and in spleen of mice at 18 months of age. . Tests of in vitro proliferation by cultured splenocytes activated by Con A or by anti-CD3 antibodies with or without anti-CD28 co- stimulation. In addition to providing assessments of immune phenotypes for tests of the three Program Aims shared by all of the projects, the data generated by Project 1 will provide answers to several questions about the relationships among T cell subsets, in vitro proliferation, and in vivo immunity in aging mice. These include; 1. Do age-sensitive T cell subset levels in peripheral blood provide a useful index of subset levels in internal lymphoid tissues? 2. Do the factors that lead to age-atypical values of any given T cell subset also regulate the levels of other age-sensitive subsets? For example, do middle-aged mice with high levels of CD4 memory cells, characteristic of advanced age, also exhibit relatively high levels of CD4M, CD4P, CD8P cells? 3. Do mice with relatively "old" levels of T cell subsets show low levels of antibody production and poor responses in tests for in vitro proliferation? In conjunction with other Projects and Cores, these tests for immune status will provide a comprehensive picture of genetic effects on age- sensitive immune traits, and will help test the idea that the pace of immune change in adult life is regulated by factors that also time age- dependent changes in other physiological domains.